Fine particulate air pollution is associated with an increased mortality due to respiratory infection and cardiovascular disease. The airway has many mechanisms to inhibit invasion and colonization of microorganisms from the environment, yet it is poorly understood how particulate air pollution affects innate immune host defenses of airway epithelium. One component of airway defense is the production of antimicrobial peptides such as (-defensins in the tracheal mucosa. In vitro and in vivo experiments have indicated a role for these peptides in the innate host defense as both direct antimicrobial agents and as chemokines that can link the innate and adaptive immune responses. Production of (-defensins in tracheal epithelial cells (TEC) is increased by bacterial lipopolysaccharide (LPS), resulting in the activation and binding of NF-(B upstream from specific (-defensin genes. Our recently published data demonstrate that low levels of an air pollutant particle, residual oil fly ash (ROFA), inhibited the LPS-mediated induction of (-defensin gene expression in cultured airway epithelial cells. This inhibition was attributed to the V2O5 composition of the particle. We hypothesize that vanadium could impair the natural host defense capability of the airway, and allow for increased colonization of the airway with bacteria. Our preliminary data show that low levels of vanadium (<2.5(g/cm2) inhibit IL-8 in addition to (-defensins in bovine and human epithelial cells. Since this in vitro observation is unexpected, given the stimulatory effect of higher concentrations (>10(g/cm2), we feel it is important to confirm the observation in vivo, prior to proposing more in-depth studies on mechanisms. We therefore hypothesize that this inhibition of bacteria-induced innate immune mediators also occurs in vivo, and will result in increased infection with Gram(+) bacteria. Demonstration in an animal model that air pollutant particles and their components can inhibit the antibacterial defenses of the lungs will allow us to develop larger studies to examine the mechanisms of the inhibition, as well as to aid in risk assessment. To address this hypothesis we propose to: 1) Determine the effect of inhaled vanadium on bacterial numbers and inflammation of the mouse airway and determine whether vanadium affects the ability of the host to combat infection through suppression of an innate immune response 2) Quantify the effect of vanadium on innate immune gene expression in mouse airways in response to bacterial infection. The long-range goal of our research is to better understand the effect of air pollutant particles on host defense. The objective of this pilot study is to confirm our in vitro results with an in vivo infection model. Successful results from this study will provide the basis for a more detailed investigation into the mechanism of pollution effects on the innate immune defense of the airway. PUBLIC HEALTH RELEVANCE: Vanadium inhalation has long been associated with infectious lung diseases in metal workers and boilermakers and recently has been implicated as a toxic component of inhaled air pollutant particles. This research studies how vanadium inhibits the initial immune response to prevent bacterial infection in the lung. We will examine the effect on mice inhaling vanadium and then infected with airway pathogens that cause pneumonia, such as Streptococcus zooepidemicus and Staphylococcus aureus. This research will help determine the mechanism and levels of inhaled vanadium necessary to suppress the initial immune response such that bacteria can colonize the airways and grow. This will help us to devise regulations for air pollutants and to determine risk for infection caused by air pollution and to devise intervention strategies.